From our efforts to identify marine natural products with cytotoxic and antitumor activity, we found an extract from a deep water marine sponge, Dragmacidon sp. Hallman, 1917,2 which inhibited the in vitro growth of P388 murine leukemia cells. The active constituent of the extract is a new bis(indo1e) alkaloid, dragmacidin (la) (6,7-dibromo-3- [5-(6-bromoindol-3-y1)-4-methyl-2 piperazinyl]-indol-4-01.~ In in vitro assays, la yielded ICw values of 15 pg/mL against P388 cells and 1-10 pg/mL against A-549 (human lung), HCT-8 (human colon), and MDAMB (human mammary) cancer cell lines. Although numerous marine natural products contain an indole or a tryptamine unit,4 few marine natural products contain two such groups, and none, to our knowledge, contains an unoxidized piperazine ring.The molecular formula of la was deduced as CzlHlg-Br3N,0 from HRFABMS and DEPT and proton-decoupled 13C NMR experiments (5 sp3 (2 d, 2 t, and 1 q) and 16 sp2 (10 s and 6 d) hybridized carbon signals observed) and requires eight double bonds and five rings.The presence of the partial structure 6-bromoindol-3-yl was suggested by the proton chemical shifts and respective coupling constants at 6 7.13 (H-5", dd, J = 1.8 and 8.6 Hz), 7.59 (H-7", d, J = 1.8 Hz), and 7.84 (H-4", d, J = 8.6 Hz). The chemical shifts and coupling constants for H-4", H-5", and H-7" are similar to those observed for eudistomin K,5 clionamide,6 and aplysinopsin-related indole^.^ Several 2D NMR experiments, including COSY,8 HETCOR,g CO-LOC,l0 and HETCOSY," facilitated complete carbon and proton assignments for C-2"-C-7" (Table I). This partial structure was supported by data from the IR and UV spectra.12 The large extinction coefficients in the UV spectrum argue for the presence of two indole chromophores in la. The presence of a second indole moiety in la was also apparent in the (LREI) mass spectral fragmentation pattern of the triacetyl derivative (lb). The base peaks observed at m/z 289/291/293, which contain two bromines, are consistent with the presence of dibromohydroxyindole (C8H5NOBr2). Further evidence for dibromohydroxyindole in la came from long-range HET-COR and HETCOSY experiments (Table I). The proton and carbon signals observed at 6 7.27 and 122.2, respectively, were assigned to C-2, and the carbon signals observed at 6 117.7, 118.2, and 138.1 were assigned to C-3a, C-3, and C-7a, respectively. In addition, the proton signal observed at 6 6.7 (s) showed direct scalar coupling to a carbon resonating at 6 110.5 (d) and long-range coupling to carbon signals observed at 6 153.1 (s), 118.5 (s), 95.6 (s), 138.1 (s).